Angelica tenuissima Nakai Ameliorates Cognitive Impairment and Promotes Neurogenesis in Mouse Model of Alzheimer's Disease

Objective: To research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics. Methods: The effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of beta-amyloid (A beta) peptide (A beta(1-42)) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open field test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in A beta(1-42)-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), A beta(1-42)] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot. Results: KH032 treatment ameliorated cognitive impairments, reduced the overexpression of A beta(1-42), and inhibited neuronal loss and neuroinflammatory response in the A beta(1-42)-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling. Conclusions: KH032 attenuated cognitive deficits in the A beta(1-42)-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.